Over the last four years, The University of Cincinnati College of Medicine has made a major commitment to the study of mouse models of gastrointestinal cancer through its participation in the Mouse Models of Human Cancers Consortium. Our previous work has led to the development of mouse models of ulcerative-colitis-associated colon cancer, pancreatic adenocarcinoma, and invasive intestinal tumors, as well as the identification of a genetic risk factor for human colorectal cancer through study of a novel mouse model with chromosomal instability. We remain focused on understanding the mechanisms that lead to the disruption of normal growth regulation in the epithelium of the gastrointestinal tract and pancreas. We propose to examine these mouse models further in order to learn more about gene-environment interactions, chemoprevention, the role of genomic instability in tumor susceptibility, the genomic and gene expression changes associated with tumor progression and invasion, and systems biology approaches to cancer genomic analyses. Our goal is to facilitate gene discovery and understand the genetic and environmental factors that influence tumor formation in the mouse in order to improve presymptomatic diagnosis, detection and treatment of human cancer.